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Symposium on Epigenetics of Cancer and Stem Cells - February 27-28, 2012, Toronto, Canada

This symposium is the fifth in a series sponsored by the SGC. Past symposia have focused on general mechanisms of epigenetic regulation, the role of epigenetics in inflammation, and environmental interactions with the human epigenome.

Postdoctoral Fellow Position in Epigenetics Chemical Biology

The Toronto site of the SGC seeks adventurous, motivated scientists to work on epigenetic histone modifying proteins and small molecule probes/inhibitors. The successful candidates will identify small molecule inhibitors using in-vitro assays, characterize these chemical probes in cellular systems, and use the probes to understand epigenetic mechanisms in normal human cellular and disease models.  

Closing Date: 
Wednesday, November 30, 2011

Contacting SGC Toronto

Our fill mailing address is:

SGC
Univerity of Toronto
MaRS South Tower, Suite 700
101 College Street
Toronto, ON M5G 1L7
Canada

Telephone: 416-946-3795

E-mail: krysia [dot] ogilvie[at]utoronto [dot] ca

How to get to SGC Toronto

The Drug Discovery Unit at the University of Dundee identifies new N-myristoyltransferase inhibitors as leads to treat sleeping sickness

09/28/2011 - 12:14

"Sleeping sickness", also known as human African trypanosomiasis, is responsible for approximately 30,000 deaths each year and 70 million people are at risk of infection, as estimated by the World Health Organization

Opening the gates for a new therapeutic opportunity in the fight against apicomplexan parasites

09/28/2011 - 12:10

Apicomplexan parasites are a diverse group of protozoan parasites, several of which cause important human and animal diseases, such as malaria, cryptosporidiosis and toxoplasmosis

Cerep to build epigenetics screening and profiling laboratory in Toronto

09/27/2011 - 22:39

The Structural Genomic Consortium (SGC) announced  today  that  SGC and  Cerep, a worldleading biotechnology company, will enter into a collaboration to develop open access biochemical and cell-based  assays for the discovery of small molecule chemical probes and drug candidates on epigenetic targets. As part of the collaboration, Cerep will open a laboratory in Toronto from which it will offer its screening and profiling services.

SGC Toronto Chief Scientist

Cheryl H. Arrowsmith Ph.D.

Research Informatics

Group Picture: 

The primary activity of the group is to apply computational chemistry tools, target-based rational, and medicinal chemistry thinking to support the development of chemical probes, with particular focus on epigenetics related targets. The team also manages the wealth of biological and chemical data generated at SGC-Toronto, and offers expertise and solutions to Information Technology related matters.

Group Member Image and Bio: 
Matthieu Schapira

Matthieu holds a M.Sc degree in chemistry from the National Superior Chemistry School, Nancy, France, and a Ph.D in biochemistry from Ecole Normale Superieure, Paris. After graduating in 1995, he completed a couple post-docs in protein crystallography and computational chemistry at New York University Medical Center. In 2000, he joined Molsoft, a San-Diego based biotech, as senior research scientist. In 2003, he moved to Lyon, France, to lead structure-based drug design at Aptanomics/Imaxio, a drug discovery start-up. In 2007, he joined the SGC as head of research informatics. Matthieu holds an Associate Professor cross-appointment with the Department of Pharmacology and Toxicology at University of Toronto, and an adjunct Associate Professor position with the Department of Pharmacology at New York University.

Emily Denton

Emily is an undergraduate student at the University of Toronto studying Computer Science and Cognitive Science with a focus in artificial intelligence. She is interested in learning and inference in both biological and artificial neural systems as well as applications of machine learning and, more broadly AI in general, to a variety of domains. This latter interest, as well as her desire to learn about and work in an exciting and highly relevant field has helped lead her to a position as a co-op student at the SGC.

Lihua Liu

Lihua received her Master's degree in computer science from State University of New York at Stony Brook in 2003. She then worked for SUNY at Stony Brook and Cold Spring Harbor Laboratory as application developer. Lihua joined SGC in 2007 as Informatics Programmer.

Kong Nguyen

Kong received his PhD from University of Berne in Switzerland with Prof. Jean-Louis Reymond in 2009. He then moved to University of California San Francisco for a postdoc with Prof. Brian Shoichet and Prof. John Irwin. Currently he is a postdoc fellow in the Research Informatics group at SGC Toronto. Kong enjoys doing molecular docking, computational biology and chemoinformatics.

Group Leader: 

Matthieu Schapira

Group Publications: 
  • Arrowsmith CH, Bountra C, Fish PV, Lee K, Schapira M - Nat Rev Drug Discov. 2012 Apr 13 - Epigenetic protein families: a new frontier for drug discovery pubmed

  • Santiago C, Nguyen K, Schapira M - J Comput Aided Mol Des. 2011;(12):1171-8 - Druggability of methyl-lysine binding sites pubmed
     
  • Schapira M - Handb Exp Pharmacol. 2011;(206):225-40 - Structural biology of human metal-dependent histone deacetylases pubmed
     
  • Schapira M - Current Chemical Genomics 2011;(5):85:94 - Structural chemistry of human SET domain protein methyltransferases pubmed
     
  • Artz JD, Wernimont AK, Allali-Hassani A, Zhao Y, Amani M, Lin YH, Senisterra G, Wasney GA, Fedorov O, King O, Roos A, Lunin VV, Qiu W, Finerty P Jr, Hutchinson A, Chau I, von Delft F, Mackenzie F, Lew J, Kozieradzki I, Vedadi M, Schapira M, Zhang C, Shokat K, Heightman T, Hui R - BMC Genomics. 2011 Sep 30;12(1):478 - The Cryptosporidium parvum kinome pubmed
     
  • Wallach I, Jaitly N, Nguyen K, Schapira M, Lilien RH - J Chem Inf Model. 2011 Aug 22;51(8):1817-30 - Normalizing molecular docking rankings using virtually generated decoys pubmed
     
  • Campagna-Slater V, Mok MW, Nguyen KT, Feher M, Najmanovich R, Schapira M - J Chem Inf Model. 2011 Mar 28;51(3):612-23 - Structural chemistry of the histone methyltransferases cofactor binding site pubmed
     
  • Yap DB, Chu J, Berg T, Schapira M, Cheng SW, Moradian A, Morin RD, Mungall AJ, Meissner B, Boyle M, Marquez VE, Marra MA, Gascoyne RD, Humphries RK, Arrowsmith CH, Morin GB, Aparicio SA - Blood. 2011 Feb 24;117(8):2451-9 - Somatic mutations at EZH2 Y641 act dominantly through a mechanism of selectively altered PRC2 catalytic activity, to increase H3K27 trimethylation pubmed
     
  • Turgeon Z, Jørgensen R, Visschedyk D, Edwards PR, Legree S, McGregor C, Fieldhouse RJ, Mangroo D, Schapira M, Merrill AR - Antimicrob Agents Chemother. 2011 Mar;55(3):983-91 - Newly Discovered and Characterized Antivirulence Compounds inhibit Bacterial Mono-ADP-ribosyltransferase Toxins pubmed
     
  • Artz JD, Wernimont AK, Dunford JE, Schapira M, Dong A, Zhao Y, Lew J, Russell RG, Ebetino FH, Oppermann U, Hui R - J Biol Chem. 2011 Feb 4;286(5):3315-22 - Molecular characterization of a novel geranylgeranyl pyrophosphate synthase from Plasmodium parasites pubmed
     
  • Kaustov L, Quyang H, Amaya M, Lemak A, Nady N, Duan S, Wasney G, Li Z, Vedadi M, Schapira M, Min J, Arrowsmith CH - J Biol Chem. 2011 Jan 7;286(1):521-9 - Recognition and specificity determinants of the human Cbx chromodomains pubmed
     
  • Wang M, Mok MW, Harper H, Lee WH, Min J, Knapp S, Oppermann U, Marsden B, Schapira M - Bioinformatics. 2010 Oct 15;26(20):2629-30 - Structural Genomics of Histone Tail Recognitionpubmed
     
  • Campagna-Slater V, Schapira M. - Molecular Informatics 2010, 29:322-331 - Finding inspiration in the Protein Data Bank to chemically antagonize readers of the histone code journal
     
  • Zhao R, Leung E, Schapira M, Houry WA - PLoS One. 2010 Apr 1;5(4):e9934 - Tamoxifen enhances the Hsp90 molecular chaperone ATPase activity pubmed
     
  • Schapira M - Burger's Medicinal Chemistry, Drug Discovery and Development, 2010 - Structural genomics, its application in Chemistry, Biology, Medicine, and Drug Discovery book chapter
     
  • Campagna-Slater V, Arrowsmith AG, Zhao Y, Schapira M. - J Chem Inf Model. 2010 Feb; 50:358-367. - Pharmacophore screening of the Protein Data Bank for specific binding site chemistrypubmed - (in top 10 list of most accessed JCIM articles, first and second quarters 2010)
     
  • Wu H, Min J, Lunin VL, Antoshenko T, Dombrovski L, Zeng H, Allali-Hassani A, Campagna-Slater V, Vedadi M, Arrowsmith CH, Plotnikov AN, Schapira M. - PLoS One. 2010 Jan 11;5(1):e8570 - Structural biology of human H3K9 Methyltransferases pubmed
     
  • Campagna-Slater V, Schapira M. - J Chem Inf Model. 2009 Sep;49(9):2082-91 - Evaluation of virtual screening as a tool for chemical genetic applications pubmed - faculty of 1000
     
  • Allali-Hassani A, Wasney GA, Chau I, Hong BS, Senisterra G, Loppnau P, Shi Z, Moult J, Edwards AM, Arrowsmith CH, Park HW, Schapira M, Vedadi M. - Biochem J. 2009 Oct 23;424(1):15-26 - A survey of proteins encoded by non-synonymous SNPs reveals a significant fraction with altered stability and activity pubmed
     
  • Guo Y, Nady N, Qi C, Allali-Hassani A, Zhu H, Pan P, Adams-Cioaba MA, Amaya MF, Dong A, Vedadi M, Schapira M, Read RJ, Arrowsmith CH, Min J. - Nucleic Acids Res. 2009 Apr;37(7):2204-10 - Methylation-state-specific recognition of histones by the MBT repeat protein L3MBTL2 pubmed
     
  • Qiu W, Wernimont A, Tang K, Taylor S, Lunin V, Schapira M, Fentress S, Hui R, Sibley LD. - EMBO J. 2009 Apr 8;28(7):969-79 - Novel structural and regulatory features of rhoptry secretory kinases in Toxoplasma gondii pubmed
     
  • Poondra RR, Kumar NN, Bijian K, Prakesch M, Campagna-Slater V, Reayi A, Reddy PT, Choudhry A, Barnes ML, Leek DM, Daroszewska M, Lougheed C, Xu B, Schapira M, Alaoui-Jamali MA, Arya P. - J Comb Chem. 2009 Jan 15 - Discovery of Indoline-Based, Natural-Product-like Compounds as Probes of Focal Adhesion Kinase Signaling Pathways pubmed
     
  • Huang X, Finerty P Jr, Walker JR, Butler-Cole C, Vedadi M, Schapira M, Parker SA, Turk BE, Thompson DA, Dhe-Paganon S. - J Struct Biol. 2009 Feb;165(2):88-96 - Structural insights into the inhibited states of the Mer receptor tyrosine kinase pubmed
     
  • Prakesch M, Bijian K, Campagna-Slater V, Quevillon S, Joseph R, Wei CQ, Sesmilo E, Reayi A, Poondra RR, Schapira M, Alaoui-Jamali M, Arya P. - Bioorg Med Chem. 2008 Nov 1;16(21):9596-602 - Building skeletally diverse architectures on the Indoline Scaffold: the discovery of a chemical probe of focal adhesion kinase signaling networks pubmed
     
  • Schuetz A, Min J, Allali-Hassani A, Schapira M, Shuen M, Loppnau P, Mazitschek R, Kwiatkowski NP, Lewis TA, Maglathin RL, McLean TH, Bochkarev A, Plotnikov AN, Vedadi M, Arrowsmith CH. - J Biol Chem. 2008 Apr 25;283(17):11355-63 - Human HDAC7 harbors a class IIa HDAC-specific zinc binding motif and cryptic deacetylase activity pubmed
     
  • Weigelt J, McBroom-Cerajewski LD, Schapira M, Zhao Y, Arrowmsmith CH. - Curr Opin Chem Biol. 2008 Feb;12(1):32-9 - Structural genomics and drug discovery: all in the family pubmed
     
  • Pamonsinlapatham P, Hadj-Slimane R, Schapira M, Samson J, Mathieu AL, Dufour S, Garbay C, Colas P - PLoS ONE. 2008 Aug 6;3(8):e2902 - A RasGAP SH3 peptide aptamer inhibits RasGAP-Aurora interaction and induces caspase-independent tumor cell death pubmed
     
  • Das S, Schapira M, Tomic-Canic M, Goyanka R, Cardozo T, Samuels HH. - Mol Endocrinol. 2007 Nov;21(11):2672-86 - Farnesyl Pyrophosphate is a Novel Transcriptional Activator for a Subset of Nuclear Hormone Receptors pubmed
     
  • Abed N, Bickle M, Mari B, Schapira M, Sanjuan-España R, Robbe Sermesant K, Moncorgé O, Mouradian-Garcia S, Barbry P, Rudkin BB, Fauvarque MO, Michaud-Soret I, Colas P - Mol Cell Proteomics. 2007 Dec;6(12):2110-21 - A comparative analysis of perturbations caused by a gene knock-out, a dominant negative allele, and a set of peptide aptamers pubmed
     
  • Schapira M, Lamigeon C, Gutmann M, Barthelaix A, Hugo N, Colas P. - EP06290821.5 (2006) - Anti-proliferative compounds deriving from a 3-aryl-coumarine or 3-aryl-quinolin-2-one and uses thereof.
     
  • Yeoun Y-J, Sackett DL, Schapira M, Walsh, Min J, Pannell LK, Chang YT - Bioorg. & Med. Chem 2006 Feb 15;14(4):1169-75. - Identification of 12Cys on tubulin as the binding site of tubulyzinepubmed
     
  • Samuels H, Abagyan R, Schapira M, Totrov M, Raaka B, Wilson S, Fan L, Zhou Z - WO2004103289 - EP20040752150 (2004) - Diverse thyroid hormone receptor antagonists and uses thereof
     
  • Anglister J, Sharon M, Schapira M, Zolla-Pazner S, Rosen O - WO2004069863 - EP20040708239 (2004) - Constrained HIV V3 loop as immunogens and receptor antagonists
     
  • Schapira M, Das S, Raaka B, Fan L, Totrov M, Wilson SR, Abagyan RA, Samuels HH - Proc Natl Acad Sci U S A. 2003; 100(12):7354-9 - Discovery of Diverse Thyroid Hormone Receptor Antagonists by High-Throughput Docking pubmed
     
  • Schapira M, Abagyan R, Totrov M - J Med Chem. 2003; 46(14):3045-59 - Nuclear Hormone Receptor Targeted Virtual Screening pubmed
     
  • Min G, Zhou G, Schapira M, Sun TT, Kong XP - J Cell Sci. 2003 Oct 15;116(Pt 20):4087-94 - Structural basis of urothelial permeability barrier function as revealed by Cryo-EM studies of the 16 nm uroplakin particle pubmed
     
  • Oxelmark E, Knoblauch R, Arnal S, Su LF, Schapira M, Garabedian MJ - J Biol Chem. 2003 Sep 19;278(38):36547-55 - Genetic dissection of p23, an Hsp90 cochaperone, reveals a distinct surface involved in estrogen receptor signaling pubmed
     
  • Schapira M. - Curr. Canc. Drug Targ 2002;2(3):243:256 - Pharmacogenomics Opportunities in Nuclear Receptor Targeted Cancer Therapy pubmed
     
  • Diwa AA, Jiang X, Schapira M, Belasco JG. - Mol Microbiol. 2002 Nov;46(4):959-69 - Two distinct regions on the surface of an RNA-binding domain are crucial for RNase E function pubmed
     
  • Schapira M, Abagyan R, Totrov M - BMC Struct Biol. 2002;2(1):1-9 - Structural model of nicotinic acetylcholine receptor isotypes bound to acetylcholine and nicotine pubmed
     
  • Harding HP, Novoa I, Zhang Y, Zeng H, Wek R, Schapira M, and Ron D - Molecular Cell 2000 Nov 17; 6:1099-1108 - Regulated translational initiation controls stress-induced gene expression in mammalian cells pubmed
     
  • Schapira M, Raaka B, Samuels HH, and Abagyan R - Proc Natl Acad Sci U S A. 2000 97(3):1008-13 Rational design of novel nuclear receptor antagonists pubmed
     
  • Schapira M, Abagyan R, Totrov M - Prediction of the binding energy for small molecules, peptides and proteins - Journal of Molecular Recognition, 1999; 12(3):177-190 pubmed
     
  • Hegde RS, Wang A-F, Kim, S-S and Schapira M - Journal of Molecular Biology, 1998, 276:797-808 - Subunit rearrangement accompanies sequence-specific DNA binding by the bovine papillomavirus-1 E2 protein pubmed
Group Contact Details: 

matthieu [dot] schapira[at]utoronto [dot] ca

416-978-3092

Group Alumni: 

A Big Thanks and Farewell to previous group members!

  • Veronica Cheung, Undergraduate Student [2007]
  • Michael De Guzman, Undergraduate Student [2008]
  • Andrew Arrowsmith, Undergraduate Student [2008-2009]
  • Valerie Campagna-Slater, Post-doctoral Fellow [2008-2010]
  • Yong Zhao, Research Associate [2007-2010]
  • Angela Mok, Undergraduate Student [2009-2010]
  • Seacy Zhen, Undergraduate Student [2009 -2010]
  • Sabrina Mota, Visiting Scientist [2010]
  • Alex Ignatchenko, Informatics Developer, Database Administrator [2008-2010]
  •  Cavin Santiago, Undergraduate Student [2010 -2011]
  • Salar Sayyad, Undergraduate Student [2010 -2011]

Biotechnology

The Biotechnology team

Group Picture: 
The Biotechnology group
Group Leader: 

Susanne Graslund

Group Member Image and Bio: 
Susanne Gräslund, PhD

Dr. Gräslund did her doctoral training at the Dept. of Biotechnology, KTH with Prof. Stefan Ståhl. After her dissertation in 2002 she worked for three years at Biovitrum AB in the Target Expression & Purification section. In March 2005, Susanne joined SGC Stockholm, heading the Biotechnology team which was responsible for the generic protein production pipeline. She was then recruited to the Toronto site as Principal Investigator for the Biotechnology team from September 2011.

Peter Loppnau, MSc
Yanjun Li, MSc

Supported by Word Health Organization, Yanjun Li did her visiting scholar training in Baylor College of Medicine for 2 years. She then worked 6 years in Stem Cell Biology Lab directed by Dr. William Stanford (IBBME, U of T), responsible for establishing gene trapping and gene targeting vectors and high throughput trapped mouse ES screenings. She transferred to Dr. Michelle Bendeck lab (LMP, U of T) in 2005 assisting supervisor in grant application, mouse protocol renewal, routine lab maintenance and transgenic mouse lines maintenance. Yanjun joined SGC Biotechnology Team as a cloner in May 2007.

Alma Seitova, PhD

Dr. Seitova obtained her PhD degree and postdoctoral position the next following years at the Dept. of Molecular Biology, Academy of Science, Moscow. After that she spent a few years at Centre "Bioengineering", (RAS).  In 2000, she joined the Cardiovascular Biology Department at OMRF, USA, where a therapeutic r-protein, Xigris, was produced using HEK293 cells. Dr. Seitova's project included production of the recombinant protein involved in blood coagulation cascade using stable and transient transfection of mammalian cells. Since 2005 she works in the Biotechnology group at SGC, currently in charge of the Eukaryotic Expression Platform.

Hao He, PhD

After three years as a general surgery doctor, Dr. Hao He did his doctoral training at the Dept. of Biochemistry and Molecular Biology, Medical school Beijing University in China. After his dissertation in 1995 he worked for three years as a post-doc at the Academy Military Medical Institute in Beijing. In Sep 1998, Dr. He moved to Sweden and worked in Department of Clinical Physics at Uppsala University for three years as a research fellow. In 2001, Dr. He moved to Canada and worked for 2 years at the Kidney Research Centre, Ottawa general Hospital. From 2003 to 2006, he worked in Dept. of Transplantation at the Toronto General Hospital for fgl2 and CD200 protein expression using Baculovirus/Insect cells and CHO cells. He then joined SGC Toronto where he is working with Baculovirus expression system in Insect cells.

Nan Zhong, PDF
Elena Dobrovetsky, MSc

Elena Dobrovetsky received her Master’s degree in Structure Determination of Biological Macromolecules by X-Ray Crystallography from Israel Technion, Schulich Faculty of Chemistry. She was then recruited to Prof.  Aled Edwards’s lab in August 2002  to work on a membrane proteins project. In 2007 she joined the Biotechnology group at SGC.

Mani Ravichandran, MSc

Mani Ravichandran did her Master's degree in Biochemistry with specialization in Clinical Biochemistry at Bharathiyar University, India. She worked as a lecturer in the Faculty of Biochemistry, Perundurai Medical College and Research Centre, India before joining the Biotechnology team at SGC Toronto in 2004. She is responsible for preparing in-house protein crystallization screens, protein purification and crystallization.

Group Publications: 

1.       Colwill K; Renewable Protein Binder Working Group; Gräslund S. A roadmap to generate renewable protein binders to the human proteome. Nat Methods. 2011 May 15;8(7):551-8. doi: 10.1038/nmeth.1607.

2.       Kotzsch A, Vernet E, Hammarström M, Berthelsen J, Weigelt J, Gräslund S, Sundström M. A secretory system for bacterial production of high-profile protein targets. Protein Sci. 2011 Mar;20(3):597-609. doi: 10.1002/pro.593

3.       Pershad K, Pavlovic JD, Gräslund S, Nilsson P, Colwill K, Karatt-Vellatt A, Schofield DJ, Dyson MR, Pawson T, Kay BK, McCafferty J. Generating a panel of highly specific antibodies to 20 human SH2 domains by phage display. Protein Eng Des Sel. 2010 Apr;23(4):279-88. Epub 2010 Feb 17

4.       Mersmann M, Meier D, Mersmann J, Helmsing S, Nilsson P, Gräslund S, Structural Genomics Consortium, Colwill K, Hust M, Dübel S. Towards proteome scale antibody selections using phage display N Biotechnol. 2010 May 31;27(2):118-28. Epub 2009 Oct 31

5.       Uhlén M, Gräslund S, Sundström M. A pilot project to generate affinity reagents to human proteins. Nat Methods. 2008 Oct;5(10):854-5.

6.   Gräslund S, Nordlund P, Weigelt J et al. Protein production and purification. Nat Methods (2008) Feb;5(2):135-46.

7.   Gräslund S, Sagemark J, Berglund H, Dahlgren LG, Flores A, Hammarström M, Johansson I, Kotenyova T, Nilsson M, Nordlund P, Weigelt J. The use of systematic N- and C-terminal deletions to promote production and structural studies of recombinant proteins. Protein Expr Purif. (2008) Apr;58(2):210-21.

Group Contact Details: 

Email: susanne [dot] graslund[at]utoronto [dot] ca

Phone: 416-978-7842

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